19-48297163-T-G

Variant names:

• chr19-48297163-T-G
• NM_001364171.2:c.1937A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364171.2(ODAD1):​c.1937A>C​(p.Tyr646Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODAD1 NM_001364171.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16409227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.1937A>C	p.Tyr646Ser	missense_variant	Exon 16 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.1826A>C	p.Tyr609Ser	missense_variant	Exon 14 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.1937A>C	p.Tyr646Ser	missense_variant	Exon 16 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461816 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.081
Sift	Benign	0.086	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.78	P
Vest4		0.22
MutPred		0.41		Gain of glycosylation at Y609 (P = 0.0158);
MVP		0.60
MPC		0.50
ClinPred		0.56	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48800420;